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Abstract
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Complexes based on heavy metals have great potential for the treatment of a wide variety of cancers
but their use is often limited due to toxic side effects. Here we describe the synthesis of two new
cadmium complexes using N(4)-phenyl-2-formylpyridine thiosemicarbazone (L1) and 5-aminotetrazole
(L2) as organic ligands and the evaluation of their anti-cancer and nephrotoxic potential in vitro.
The complexes were characterized by Single-crystal X-ray data diffraction, 1HNMR, FT-IR, LC/MS
spectrometry and CHN elemental analysis. Next, cytotoxicity of these cadmium complexes was
evaluated in several cancer cell lines, including MCF-7 (breast), Caco-2 (colorectal) and cisplatinresistant
A549 (lung) cancer cell lines, as well as in conditionally-immortalized renal proximal tubule
epithelial cell lines for evaluating nephrotoxicity compared to cisplatin. We found that both compounds
were toxic to the cancer cell lines in a cell-cycle dependent manner and induced caspase-mediated
apoptosis and caspase-independent cell death. Nephrotoxicity of these compounds was compared
to cisplatin, a known nephrotoxic drug, in vitro. Our results demonstrate that compound {2}, but not
compound {1}, exerts increased cytotoxicity in MCF-7 and A549 cell lines, combined with reduced
nephrotoxic potential compared to cisplatin. Together these data make compound {2} a likely candidate
for further development in cancer treatment.
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